Oral leukoplakia is one of the most prevalent lesions found in the oral mucosa. It presents clinically as a white thickened patch representing, in the majority of cases, an area of epithelial thickening. Etiologic factors associated with the development of leukoplakia are tobacco and alcohol use and a major concern is the 4-6% of all lesions transform into oral cancer. The hypothesis in the proposed study is that the lesion is an area in which the epithelial barrier function is impaired so that carcinogens can readily gain access to the underlying tissues. The study described in this application a collaboration between Dr. J. Banoczy, Budapest, Hungary, who is a leading authority on oral leukoplakia, and the principal investigator at the University of Iowa, who has extensively characterized the barrier properties of oral epithelia. The specific aims are (1) to determine the permeability of oral leukoplakia to a tobacco-derived carcinogen; (2) to determine the chemical components of the epithelial permeability barrier, and (3) to determine whether these parameters can be related to alcohol use. Dr. Banoczy will draw upon an extensive population of leukoplakic tissue that can be characterized in terms of clinical, etiological, and histopathological features. The tissue will then be sent to the Principal Investigator in Iowa who will measure the permeability of the tissue to a candidate tobacco carcinogen and determine the composition of barrier lipids. Data from these latter determinations will be related to the clinical, etiological, and histological parameters derived in Dr. Banoczy's laboratory so as to answer the specific aims. The studies to be undertaken represent the first attempt to provide a mechanistic explanation of the malignant potential of oral leukoplakia and has great significance for understanding and, thus, reducing risk factors for oral cancer.